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Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2).
Chey, WD, Lembo, AJ, Yang, Y, Rosenbaum, DP
The American journal of gastroenterology. 2021;(6):1294-1303
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Abstract
INTRODUCTION Tenapanor is a first-in-class, minimally absorbed, small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger isoform 3. This phase 3 trial assessed the long-term efficacy and safety of tenapanor 50 mg b.i.d. for the treatment of patients with irritable bowel syndrome with constipation (IBS-C). METHODS In this randomized double-blind study (ClinicalTrials.gov identifier: NCT02686138), patients with IBS-C received tenapanor 50 mg b.i.d. or placebo b.i.d. for 26 weeks. The primary endpoint was the proportion of patients who had a reduction of ≥30.0% in average weekly worst abdominal pain and an increase of ≥1 weekly complete spontaneous bowel movement from baseline, both in the same week, for ≥6 of the first 12 treatment weeks (6/12-week combined responder). RESULTS Of the 620 randomized patients with IBS-C, 593 (95.6%) were included in the intention-to-treat analysis set (tenapanor: n = 293; placebo: n = 300) and 481 patients (77.6%) completed the 26-week treatment period. In the intention-to-treat analysis set (mean age: 45.4 years; 82.1% women), a significantly greater proportion of patients treated with tenapanor were 6/12-week combined responders than those treated with placebo (36.5% vs 23.7%; P < 0.001). Abdominal symptoms and global symptoms of IBS were significantly improved with tenapanor compared with placebo. Diarrhea, the most common adverse event, was typically transient and mild to moderate in severity. Diarrhea led to study drug discontinuation for 19 (6.5%) and 2 patients (0.7%) receiving tenapanor and placebo, respectively. DISCUSSION Tenapanor 50 mg b.i.d. improved IBS-C symptoms over 26 weeks and was generally well tolerated, offering a potential new long-term treatment option for patients with IBS-C (see Visual abstract, Supplementary Digital Content 1, http://links.lww.com/AJG/B797).
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Effect of Three Diets (Low-FODMAP, Gluten-free and Balanced) on Irritable Bowel Syndrome Symptoms and Health-Related Quality of Life.
Paduano, D, Cingolani, A, Tanda, E, Usai, P
Nutrients. 2019;(7)
Abstract
Several studies have reported some efficacy of diets low in fermentable carbohydrates (Fermentable Oligo-, Di-, Monosaccharides and Polyols (FODMAPs)) in Irritable Bowel Syndrome (IBS). There is no evidence of its superiority compared to gluten-free and balanced diets in improving IBS patients' quality of life (QoL). The aim of this study is to assess whether different diets can improve QoL in IBS. Forty-two patients with IBS, according to Rome IV criteria, were enrolled. Low-FODMAP, gluten-free and balanced diets were proposed to each patient in the same succession. Each diet was followed for 4 weeks. The Bristol Stool Scale, the Visual Analogue Scale (VAS) for bloating and abdominal pain, and the SF12 questionnaire for health-related quality of life were applied at the beginning and at the end of each diet. Twenty-eight of the forty-two patients completed all the three diets. All the three diets reduced symptom severity (p < 0.01), bloating (p < 0.01) and abdominal pain (p < 0.01), and improved quality of life (p < 0.05); 3% of patients expressed a preference for the low-FODMAP diet, 11% for the gluten-free and 86% for the balanced diet (p < 0.01). The balanced diet improves QoL and VAS pain, provides an adequate quantity of FODMAPs and is more appreciated by patients. For these reasons, the balanced diet could be recommended to patients with irritable bowel syndrome.
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Assessment of the effectiveness and safety of ethosuximide in the treatment of abdominal pain related to irritable bowel syndrome - IBSET: protocol of a randomised, parallel, controlled, double-blind and multicentre trial.
Kerckhove, N, Scanzi, J, Pereira, B, Ardid, D, Dapoigny, M
BMJ open. 2017;(7):e015380
Abstract
INTRODUCTION Irritable bowel syndrome (IBS) is characterised by the association of abdominal chronic pain with bowel habit disorders in the absence of identifiable organic disease. This is the first reason for consultation in gastroenterology, with an estimated prevalence of 10%-15% in industrialised countries. Although this is a benign gastrointestinal disease, its chronicity profoundly impacts the patient's quality of life and causes considerable health spending. Actual medical treatments are poorly efficient on IBS-related abdominal pain, making it a major public health concern. The mechanisms causing IBS symptoms are unknown. Recent studies have shown the involvement of T-type channel in abdominal pain. We aim to evaluate the therapeutic potential of ethosuximide, a T-type channel blocker, on the abdominal pain of patients presenting an IBS. METHODS AND ANALYSIS The IBSET trial is a randomised, controlled, parallel, double-blind and multicentre study. It is the first clinical trial evaluating the efficacy and safety of ethosuximide on abdominal pain related to IBS. Adults with IBS that report significant abdominal pain (≥4/10) at least for 3 months will be included. 290 patients will be randomly assigned to receive either ethosuximide or placebo over 12 weeks after 1 week of run-in period. The primary endpoint is the rate of responders (pain reduction ≥30% and Subject Global Assessment of Relief score ≥4). The intensity of abdominal pain will be assessed by an 11-point Numerical Rating Scale before and after 12 weeks of treatment and the score of the Subject Global Assessment of Relief scale at the end of treatment. The secondary endpoints are the safety of ethosuximide, the intensity and features of IBS and quality of life. ETHICS AND DISSEMINATION The study was approved by an independent medical ethics committee (CPP Sud-Est VI, Clermont-Ferrand, France). The results will be published in a peer-review journal and presented at international congresses. TRIAL REGISTRATION NUMBER NCT02973542; Pre-results.
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Randomised controlled trial of mesalazine in IBS.
Barbara, G, Cremon, C, Annese, V, Basilisco, G, Bazzoli, F, Bellini, M, Benedetti, A, Benini, L, Bossa, F, Buldrini, P, et al
Gut. 2016;(1):82-90
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Abstract
OBJECTIVE Low-grade intestinal inflammation plays a role in the pathophysiology of IBS. In this trial, we aimed at evaluating the efficacy and safety of mesalazine in patients with IBS. DESIGN We conducted a phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800 mg, or placebo, three times daily for 12 weeks, and were followed for additional 12 weeks. The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period. The key secondary endpoint was satisfactory relief of overall IBS symptoms. Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75% or >75% of time. RESULTS A total of 185 patients with IBS were enrolled from 21 centres. For the primary endpoint, the responder patients were 68.6% in the mesalazine group versus 67.4% in the placebo group (p=0.870; 95% CI -12.8 to 15.1). In explorative analyses, with the 75% rule or >75% rule, the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6% (p=0.115; 95% CI -2.7% to 26.0%) and 5.9% (p=0.404; 95% CI -7.8% to 19.4%), respectively, although these differences were not significant. For the key secondary endpoint, overall symptoms improved in the mesalazine group and reached a significant difference of 15.1% versus placebo (p=0.032; 95% CI 1.5% to 28.7%) with the >75% rule. CONCLUSIONS Mesalazine treatment was not superior than placebo on the study primary endpoint. However, a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy. TRIAL REGISTRATION NUMBER ClincialTrials.gov number, NCT00626288.
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Irritable bowel syndrome symptom severity improves equally with probiotic and placebo.
Lyra, A, Hillilä, M, Huttunen, T, Männikkö, S, Taalikka, M, Tennilä, J, Tarpila, A, Lahtinen, S, Ouwehand, AC, Veijola, L
World journal of gastroenterology. 2016;(48):10631-10642
Abstract
AIM: To determine the effects of Lactobacillus acidophilus NCFM on irritable bowel syndrome (IBS) symptoms and quality of life (QoL). METHODS In this randomized triple-blind trial, adult IBS volunteers who were recruited according to Rome III criteria received 109 or 1010 colony-forming units of NCFM or placebo daily for 12 wk. IBS Symptom Severity Score (IBS-SSS), which constituted the primary outcome, and secondary outcomes, including individual IBS symptoms, IBS-related QoL questionnaire, anxiety and depression, defecation frequency, and stool consistency, were assessed at baseline at the end of the 8-wk run-in period, after 4 and 12 wk of intervention, and after a 4-wk washout. RESULTS A total of 340 of 391 randomized volunteers completed the trial. IBS-SSS improved over 12 wk of treatment in all treatment groups, decreasing by a mean ± SD of 44.0 ± 80.2, 50.8 ± 82.4, and 48.3 ± 72.2 in the placebo, active low-dose, and active high-dose groups, respectively. Similarly, secondary outcomes did not differ between treatment groups. However, in a post hoc analysis of volunteers with moderate to severe abdominal pain at baseline (VAS > 35/100), the treatment significantly reduced the sensation of abdominal pain. Pain scores fell by 20.8 ± 22.8, 29.4 ± 17.9, and 31.2 ± 21.9 in the placebo, active low-dose, and active high-dose groups, respectively (P value for placebo vs combined active doses = 0.0460). CONCLUSION NCFM alleviates moderate to severe abdominal pain, consistent with earlier observations of this strain mitigating visceral pain through increased analgesic receptor expression.
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Efficacy of a Gluten-Free Diet in Subjects With Irritable Bowel Syndrome-Diarrhea Unaware of Their HLA-DQ2/8 Genotype.
Aziz, I, Trott, N, Briggs, R, North, JR, Hadjivassiliou, M, Sanders, DS
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2016;(5):696-703.e1
Abstract
BACKGROUND & AIMS A gluten-containing diet alters bowel barrier function in patients with irritable bowel syndrome with diarrhea (IBS-D), particularly those who are positive for HLA allele DQ2/8. We studied the effects of a gluten-free diet (GFD) in patients with IBS-D who have not previously considered the effects of gluten in their diet and were unaware of their HLA-DQ2/8 genotype. METHODS We performed a prospective study of 41 patients with IBS-D (20 HLA-DQ2/8-positive and 21 HLA-DQ2/8-negative) at the Royal Hallamshire Hospital in Sheffield, United Kingdom, from September 2012 through July 2015. All subjects were placed on a 6-week GFD following evaluation by a dietician. Subjects completed validated questionnaires at baseline and Week 6 of the GFD. The primary endpoint was mean change in IBS Symptom Severity Score; a 50-point reduction was considered to indicate a clinical response. Secondary endpoints were changes in hospital anxiety and depression score, fatigue impact score, and Short Form-36 results. Clinical responders who chose to continue a GFD after the study period were evaluated on average 18 months later to assess diet durability, symptom scores, and anthropometric and biochemical status. RESULTS A 6-week GFD reduced IBS Symptom Severity Score by ≥50 points in 29 patients overall (71%). The mean total IBS Symptom Severity Score decreased from 286 before the diet to 131 points after 6 weeks on the diet (P < .001); the reduction was similar in each HLA-DQ group. However, HLA-DQ2/8-negative subjects had a greater reduction in abdominal distention (P = .04). Both groups had marked mean improvements in hospital anxiety and depression scores, fatigue impact score, and Short Form-36 results, although HLA-DQ2/8-positive subjects had a greater reduction in depression score and increase in vitality score than HLA-DQ2/8-negative subjects (P = .02 and P = .03, respectively). Twenty-one of the 29 subjects with a clinical response (72%) planned to continue the GFD long term; 18 months after the study they were still on a GFD, with maintained symptom reductions, and demonstrated similar anthropometric and biochemical features compared with baseline. CONCLUSIONS A dietitian-led GFD provided sustained benefit to patients with IBS-D. The symptoms that improved differed in magnitude according to HLA-DQ status. Clinical trials.gov no: NCT02528929.
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[Treating irritable bowel syndrome by wuling capsule combined pinaverium bromide: a clinical research].
Wu, XW, Hou, Y, Ji, HZ, Liang, MM, Xu, LE, Wang, FY
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine. 2015;(4):415-8
Abstract
OBJECTIVE To evaluate the efficacy and safety of wuling Capsule combined with Pinaverium Bromide in treatment of irritable bowel syndrome (IBS). METHODS Sixty-four IBS patients were randomized into two groups, the treatment group and the control group, 32 in each group. Patients in the treatment group took wuling Capsule (0. 33 g/capsule, 3 times per day) and Pinaverium Bromide (50 mg/tablet, one tablet each time, 3 times per day) , while those in the control group only took Pinaverium Bromide (50 mg/tablet, one tablet each time, 3 times per day). The therapeutic course for all was 6 weeks. IBS symptom score questionnaire, IBS-Quality of Life (IBS-QOL) , Self-Rating Depression Scale (SDS) , and Self-Rating Anxiety Scale (SAS) were assessed before and after treatment. Adverse reactions were also observed. RESULTS The improvement of abdominal pain, stool frequency, and stool properties, as well as changing rates of integrals were significantly higher in the treatment group than in the control group (P <0. 05). The improvement of dysphoria, body image, concerns for health, and dietary restriction of IBS-QOL, as well as changing rates of integrals were significantly higher in the treatment group than in the control group (P <0. 05). The improvement of SDS and SAS, as well as changing rates of integrals were significantly higher in the treatment group than in the control group (P <0. 05). No severe adverse reaction occurred in either group. CONCLUSION Combination therapy of wuling Capsule and Pinaverium Bromide could improve abdominal pain and defecation, attenuate depression and anxiety of IBS patients with higher safety.
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Interaction between preprandial and postprandial rectal sensory and motor abnormalities in IBS.
Törnblom, H, Van Oudenhove, L, Tack, J, Simrén, M
Gut. 2014;(9):1441-9
Abstract
BACKGROUND AND AIMS Rectal sensory and motor interactions in patients with IBS have not been studied in detail. The aim of this study was to evaluate fasting and postprandial rectal sensorimotor characteristics and their interactions in IBS compared with healthy controls. DESIGN We included 274 patients with IBS and 34 controls. All subjects underwent a rectal barostat study before and 60 min after a standardised liquid meal (800 kcal; 60% fat). Sensory thresholds, intensity of sensations, viscerosomatic referral and compliance were measured. During 15 min before the first distension sequence and until 50 min after meal intake, rectal balloon volumes were registered in 5 min intervals at operating pressure to quantify rectal tone. Mixed models were used to analyse the rectal tone response over time. RESULTS Rectal sensory thresholds and compliance were decreased and viscerosomatic referral areas increased in patients with IBS compared with controls. Meal intake increased rectal sensitivity, compliance and referral areas in patients and controls and the same proportions of patients were hypersensitive to distension before and after meal intake. There was a higher basal rectal tone in IBS and a significantly different rectal tone response after meal intake in patients with IBS compared with controls and, interestingly, also in IBS with rectal hypersensitivity (defined in the preprandial state), compared with normosensitive patients. CONCLUSIONS Meal intake affects rectal sensorimotor function in IBS and health. Importantly, the rectal tone responses to a high-caloric meal are different between patients with IBS and controls, as well as between hypersensitive and normosensitive patients with IBS.
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Effect of capsule 'UB03' containing potential probiotic strains for the treatment of patients with irritable bowel syndrome.
Sudha, MR, Sawant, P
Beneficial microbes. 2011;(3):229-33
Abstract
The objective of this research was to study the efficacy and safety of capsule 'UB03' to treat patients with Irritable Bowel Syndrome (IBS). Thirty patients with Rome II IBS were assigned to receive capsule 'UB03' (10 billion lyophilised bacteria and yeast/capsule produced by Unique Biotech Limited, India) twice daily for 90 days. Assessment of IBS was carried out according with Rome II criteria and their severity for 90 days of treatment with an interval of 30 days. Complete haemogram, serum glutamic pyruvic transaminase, serum creatinine were performed as a part of safety evaluation at the time of inclusion and after 90 days of treatment. There was significant improvement in frequency of defecation (23%), consistency of stool, abdominal discomfort, bloating and flatulence. However, there was no significant change in abdominal pain and mucus in stool. This trial demonstrates that the consumption of capsule 'UB03' containing potential probiotic strains is found to be effective and safe for the treatment of patients with IBS.
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Probiotic treatment of irritable bowel syndrome in children.
Martens, U, Enck, P, Zieseniss, E
German medical science : GMS e-journal. 2010;:Doc07
Abstract
UNLABELLED Treatment of functional bowel disorders of irritable bowel-type (IBS) in children remains a difficult task because of a lack of drugs with low adverse event profile. We here report the results of a treatment study in 203 children (66 boys and 137 girls) age 4 to 18 years (mean: 10.5+/-4.5 years) with typical IBS symptoms with abdominal pain and either predominant diarrhea (n=50), constipation (n=56), alternating stool frequency (n=28) or unspecific pain (n=69). The average duration of symptoms prior to therapy was 175 days. Most (95%) patients up to age 11 were treated with a daily dose of 10 drops of Symbioflor 2 (SF2) (SymbioPharm, Herborn) (cells and autolysate of 1.5-4.5x10(7) CFU of bacteria of Escherichia coli type), in the elder children 77% received this dosage, while the remaining received a higher dose up to 30 drops/day. Treatment lasted 43 days on average. RESULTS All patients tolerated the treatment well and without adverse events. The key IBS symptoms (abdominal pain, stool frequency) as well as the other symptoms (bloating, mucous and blood in stool, need for straining at stools, urge to defecate) improved significantly during treatment. Global assessment of therapy by parents and doctors was altogether positive. In summary these data confirm efficacy and tolerability of this probiotic compound in children and adolescents and supplement published data of probiotic IBS therapy in adults.